Now new research on mice provides clues to how excess body fat harms the human brain — and how exercise may help combat obesity-related cognitive decline.

Scientists at the Georgia Regents University in Augusta, Ga., found that obese mice displayed poor brain function and diminished memory compared to leaner rodents. The research, published in The Journal of Neuroscience, indicated that excess body fat had a harmful effect, whether the mice overate their way to obesity or had fat pads surgically implanted in their bodies.

According to the study, the cognitive decline resulted from inflammation-causing substances secreted by fat cells being released into the blood stream. These substances, known as inflammatory cytokines, can bypass the blood-brain barrier. As Gretchen Reynolds explains in a recent New York Times Well post:

In these mice, as interleukin 1 migrated to the head, it passed the blood-brain barrier and entered areas such as the hippocampus, a part of the brain critical for learning and memory. There, it essentially gummed up the works, the researchers found when they examined tissue from the animals’ brains, which had high levels of interleukin 1 together with widespread markers of inflammation. While inflammation can represent a healthy response to invading molecules, it hurts cells if it persists.

The researchers also noted extremely low levels in these mice brains of a biochemical associated with healthy synapse function. Synapses are the structures that connect one neuron to another and shunt messages between them. Healthy synapses respond to demands on the brain by slowing or speeding messages, keeping the brain’s nervous-system traffic manageable. But low levels of the marker of synapse health suggested to the researchers that in these obese animals’ inflamed brains, synapses were no longer functioning properly and messages between neurons likely jerked, hiccuped or stalled.

To determine whether excess fat was the primary physiological factor behind the cognitive decline, the researchers surgically removed the fat from the mice. The findings were convincing: Post-recovery cognitive tests showed almost no interleukin 1 and that normal brain function was largely restored.

Surgery, however, is not a realistic route to weight loss for many people, so the researchers explored a less-invasive and more accessible alternative: exercise. For nearly three months, a test group of mice ran on a treadmill for 45 minutes a day.

After 12 weeks, the mice’s weight didn’t change compared to that of the non-exercising mice, but they did lose fat and gain lean muscle. And when the researchers tested the mice’s cognitive function, they found the exercised mice performed better than their sedentary counterparts, leading them to to conclude that cognitive decline could also be reversed with regular exercise.

While the results are intriguing, it’s unclear how these strategies might impact cognitive decline in humans. Still, there are a few things we do know about brain health, including that maintaining a healthy weight is good for memory function:

Previous research has shown that overweight people have a harder time recalling episodic memories — like a first date or a childhood trip to the Grand Canyon — and that this memory process can improve with weight loss. Studies suggest that this enhanced brain function is a result of better insulin resistance, which can be hampered by obesity. Insulin sensitivity can be modulated by diet and lifestyle, and as it improves, so does brain function. — “Weight Loss, Memory Gain” (Experience Life, January/February 2014)

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